PI3K/Akt信号通路在白藜芦醇抗大鼠缺血/再灌注性心律失常中的作用及机制  

A study on anti-arrhythmia mechanisms of resveratrol on ischemia/reperfusion in rats by regulating PI3K/Akt signaling pathway

作　　者：宋娟[1] 王佳[2] 李宝红[1] 王东[3] 孟董超 卢彦珍[1] SONG Juan WANG Jia LI Bao-hong WANG Dong MENG Dong-chao LU Yan-zhen(Depamnent of Pathophysiology Department of Immunology Department of Reform of Education and Teaching Class of 2013 year, Changzhi Medical College, Changzhi 046000, China)

机构地区：[1]长治医学院病理生理学教研室,山西长治046000 [2]长治医学院免疫学教研室,山西长治046000 [3]长治医学院教改班2013级,山西长治046000

出　　处：《中国应用生理学杂志》2017年第3期239-243,共5页Chinese Journal of Applied Physiology

基　　金：山西省2013年国家级大学生创新创业训练资助项目(2013083);长治医学院科技启动基金资助项目(QDZ201520);长治医学院大学生创新创业训练计划项目(D2016001)

摘　　要：目的:探讨磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号通路在白藜芦醇抗缺血/再灌注性心律失常中的作用及机制。方法:48只健康雄性SD大鼠,取心电图正常者随机分为4组(n=10):假手术(SC组)组、缺血/再灌注(I/R组)组、白藜芦醇处理(Res处理组)组、PI3K抑制剂LY294002(LY294002组)组。建立大鼠在体心肌缺血/再灌注模型,观察各组心律失常的发生情况及左室血流动力学变化,Western blot法测定心肌组织中蛋白激酶B(Akt)、磷酸化蛋白激酶B(p-Akt)、缝隙连接蛋白43(Cx43)蛋白表达水平,以RT-PCR法从转录水平检测Cx43的表达水平。结果:与I/R组相比,Res处理组心律失常的发生率(心律失常评分)明显降低、左室舒缩功能明显升高,同时心肌Akt、Cx43蛋白表达及Cx43m RNA水平也明显升高;使用PI3K抑制剂LY294002后,心肌Akt、Cx43蛋白表达及Cx43m RNA水平下降的同时心律失常的发生率明显升高、左室舒缩功能明显降低。结论:白藜芦醇的抗再灌注性心律失常作用可能是通过激活PI3K/Akt信号通路,改变Cx43活性及分布实现的。Objective： To investigate whether the phosphatidyl-inositol-3-kinase/protein kinase B（PI3K/Akt）pathway is involved in anti-arrhythmia of resveratrol on ischemia/reperfnsion in rat hearts. Methods： Forty male rats of normal ECG were randomly divided into 4 groups （n=10）： sham control （SC） group, ischemic/reperfusion （I/R） group, resveratrol （Res） group, PI3K inhibitor LY294002 （LY294002） group. The rat myocardial I/R injury model was established in vivo. The arrhythmia and left ventricular functional parameters including left ventricular pressure （LVP）, left ventricular systolic pressure （LVSP） and its derivate （± dp/dtmax） were measured; the protein levels of total Akt, phosphorylated Akt and counexin 43 （Cx43） were measured by Western blot; the mRNA level of Cx43 was detected by Real-time PCR. Results： The phosphorylated levels of Akt and myocardial Cx43 were significantly enhanced in Res group as compared with I/R group（ P 〈 0. 01 ） ; whereas the incidence rate of induced ventricular reperfusion arrhythmias was significantly lower, the left ventricular function was evident- ly enhanced. After addition of PI3K inhibitor LY29d002, the protein and mRNA levels of Akt and Cx43 were decreased in LY294002 group, while the incidence rate of reperfusion arrhythmias was significantly higher and the left ventricular function were evidently damaged compared with Res group（ P 〈0. 01）. Conclusion： Resveratrol could prevent the occurrence of reperfusion arrhythmias by increasing the content and activity of myocardial Cx43 through the PI3K/Akt signaling pathway.

关 键 词：白藜芦醇 再灌注性心律失常 PI3K/AKT信号转导通路 缝隙连接蛋白43 大鼠 

分 类 号：R541.7[医药卫生—心血管疾病]